SARS-CoV-2 Spike Mutations Modify the Interaction Between Virus Spike and Human ACE2 Receptors

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COVID-19, Sars-cov-2, Mutation, Spike Protein, Interface Residues

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The high mutability of the SARS-CoV-2 virus is a growing concern among scientific communities and health professionals since it brings the effectiveness of repurposed drugs and vaccines for COVID-19 into question. Although the mutational investigation of the Spike protein of the SARS-CoV-2 virus has been confirmed by many different researchers, there is no thorough investigation carried out at the interacting region to reveal the mutational status and its associated severity. All the energetically favorable mutations and their detailed analytical features that could impact the infection severity of the SARS-CoV-2 virus need to be identified. Therefore, we have thoroughly investigated the most important site of the SARS-CoV-2 virus, which is the interface region (Residue 417–505) of the virus Spike that interacts with the human ACE2 receptor. Further, we have utilized molecular dynamic simulation to observe the relative stability of the Spike protein with partner ACE2, as a consequence of these mutations. In our study, we have identified 52 energetically favorable Spike mutations at the interface while binding to ACE2, of which only 36 significantly enhance the stabilization of the Spike-ACE2 complex. The stability order and molecular interactions of these mutations were also identified. The highest stabilizing mutation V503D confirmed in our study is also known for neutralization resistance.

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Biochemical and Biophysical Research Communications, v. 620, p. 8-14